title: Genetic isolation and characterization of a splicing mutant of zebrafish dystrophin.
abstract: Sapje-like (sap(cl100)) was one of eight potential zebrafish muscle mutants isolated as part of an early-pressure screen of 500 families. This mutant shows a muscle tearing phenotype similar to sapje (dys-/-) and both mutants fail to genetically complement suggesting they have a mutation in the same gene. Protein analysis confirms a lack of dystrophin in developing sapje-like embryos. Sequence analysis of the sapje-like dystrophin mRNA shows that exon 62 is missing in the dystrophin transcript causing exon 63 to be translated out of frame terminating translation at a premature stop codon at the end of exon 63. Sequence analysis of sapje-like genomic DNA identified a mutation in the donor splice junction at the end of dystrophin exon 62. This mutation is similar to splicing mutations associated with human forms of Duchenne Muscular Dystrophy. Sapje-like is the first zebrafish dystrophin splicing mutant identified to date and represents a novel disease model which can be used in future studies to identify therapeutic compounds for treating diseases caused by splicing defects.
authors.affiliation: Division of Genetics, Children's Hospital, Boston, MA, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Guyon
authors.forename: Julie
authors.initials: J
authors.lastname: Goswami
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Jun
authors.forename: Marielle
authors.initials: M
authors.lastname: Thorne
authors.forename: Melanie
authors.initials: M
authors.lastname: Howell
authors.forename: Timothy
authors.initials: T
authors.lastname: Pusack
authors.forename: Genri
authors.initials: G
authors.lastname: Kawahara
authors.forename: Leta S
authors.initials: LS
authors.lastname: Steffen
authors.forename: Michal
authors.initials: M
authors.lastname: Galdzicki
authors.forename: Louis M
authors.initials: LM
authors.lastname: Kunkel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D004195:Disease Models, Animal; D016189:Dystrophin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D012326:RNA Splicing; D016415:Sequence Alignment; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D016189:Dystrophin; D029961:Zebrafish Proteins